Serotonin-containing neurons: their possible role in pain and analgesia

Abstract

Experimental evidence is reviewed showing that brain and spinal cord serotonergic neurons are involved in nociceptive responses, as well as in the analgesic effects of opiate narcotics. This evidence, based on studies employing pharmacological, surgical, electrophysiological, and dietary manipulations of central nervous system serotonergic neurotransmission, suggests that increases in the activity of brain and spinal cord serotonin neurons are associated with analgesia and enhanced antinociceptive drug potency, whereas decreases in the activities of these neurons correlate with hyperalgesia and diminished analgesic drug potency.

Effects of graded oral doses of a new 5‐hydroxytryptamine/noradrenaline uptake inhibitor (Ro 15‐8081) in comparison with 60 mg codeine and placebo on experimentally induced pain and side effect profile in healthy men.

“…Since the tail flick response is a spinal reflex (Irwin etal., 1951), while the hot plate response is integrated at higher supraspinal levels (Hayes et al, 1978) and includes escape behaviours requiring a high degree of sensorimotor integration, these findings suggest that the antinociceptive effects of Ro 15-8081 are mediated by mechanisms involving the central nervous system. This has to be expected also in the light of studies showing that increased levels of 5-HT (Messing & Lytle, 1977) and/or noradrenaline in the brain and in the spinal cord, as occurring after the administration of drugs inhibiting 5-HT and noradrenaline reuptake, potentiate activity in descending serotoninergic and noradrenergic bulbo-spinal neurons which control spinal processing of nociceptive information and thus lead to hypoalgesia (Duggan, 1985). Ro 15-8081 is structurally unrelated to opioids, acts neither agonistic nor antagonistic at opioid receptor sites and its antinociceptive effects are not antagonized consistently by naloxone.…”

“…mean from basal values (A ms) 30,60,90,120,150,180,210,240,270,300,330, and 360 min after administration of 50 mg Ro 15-8081 ( ), 25 mg Ro 15-8081 (--), 10 mg Ro 15-8081 (----), 60 mg codeine (-), and placebo ( ---). (Messing & Lytle, 1977). However, mixed 5-HT/noradrenaline uptake inhibitors seem to be superior in analgesic activity to selective 5-HT uptake inhibitors.…”

Serotonin Neurotoxicity after (±)3,4-Methylenedioxymethamphetamine (MDMA; “Ecstasy”): A Controlled Study in Humans

“…Because 5-HT has been impli cated in central pain (see Richardson 1992), and because impairments in 5-HT function have been associated with alterations in nociception (see Messing and Lytle 1977), pain measures were also examined in MDMA users. Nociceptive function was assessed by the sub maximum-effort tourniquet technique for inducing isch emic pain in humans (Smith et al 1966).…”

On the Role of 5‐hydroxytryptamine in Drug‐induced Antinociception

“…There is considerable evidence to suggest that the antinociceptive effect of morphine is dependent upon intact central 5-hydroxytryptaminergic pathways (Messing & Lytle, 1977;Sewell & Spencer, 1977). The elevation of brain content of 5-hydroxytryptamine (5-HT) either by the intracerebroventricular (i.c.v.)…”